RESUMO
Flumazenil is a competitive inhibitor of the specific biding of benzodiazepines to central nervous system receptor sites and it is valuable in reversing their sedative effect. Twenty-four healthy patients (ASA I and II), both male and female, with age between 19 and 58 years and weight between 46 and 79 kg, scheduled for elective surgery under flunitrazepam oral premedication and intravenous sedation after spinal anesthesia, were submitted to a trial with flumazenil for reversal of sedation. Judged by the degree of sedaation, comprehension, cooperation and time and space orientation, flumazenil showed good results. Only 12 por cent of the patients presented resedation after 120 minutes. No adverse effect was observed.
Assuntos
Humanos , Adulto , Período de Recuperação da Anestesia , Anestesia Epidural , Flumazenil/uso terapêutico , Flunitrazepam/efeitos adversos , Flunitrazepam/antagonistas & inibidoresRESUMO
A phase 1 double blind crossover comparison of a new benzodiazepine antagonist (Ro 15-3505) with Ro 15-1788 and placebo, in the reversal of sedative and psychophysiological effects of single IV doses of flunitrazepam (2 mg), was carried out in 12 normal volunteers. The antagonists were equally effective, leading to full reversal of all effects with a potency ratio of approximately 2.5 mg Ro 15-1788 for 1 mg Ro 15-3505. Inverse agonism, in the form of unpleasant feelings and symptoms, was reported by all subjects following Ro 15-3505 but none after Ro 15-1788. Adaptational phenomena such as acute tolerance and rebound of sedative effects of flunitrazepam were also detected and their potential implications are discussed.
Assuntos
Benzodiazepinas/antagonistas & inibidores , Benzodiazepinonas/farmacologia , Flumazenil/farmacologia , Flunitrazepam/antagonistas & inibidores , Adulto , Atenção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Tolerância a Medicamentos , Eletroencefalografia , Flunitrazepam/sangue , Humanos , Injeções Intravenosas , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacosRESUMO
The amnestic effects of flunitrazepam (2 mg intravenously) were studied in normal volunteers with emphasis on their relationship to sleep and their reversal by two specific benzodiazepine receptor antagonists (Ro 15-1788 and Ro 15-3505). The test battery was based on available clinical tests to assess various aspects of encoding and recall. The results suggest that flunitrazepam impairs acquisition of new information by interfering with encoding, and that these effects are clearly independent of sleep. Flunitrazepam effects on memory were fully reversed by both antagonists, as were the subjective and objective signs of sedation. This speaks against the hypothesis of different receptors for sedative and amnestic effects. Ro 15-3505 had shorter lasting effects than Ro 15-1788 and interfered with some tests; this is discussed in relation to its inverse agonistic effects.